Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2 cells

Abstract

The multiple toxic effects of ochratoxin A (OTA) are a threat for human and animal. This study aimed to examine whether B. subtilis CW14 protected against OTA-induced barrier disruption and cell damage to Caco-2 cells. The results showed that Caco-2 cells treated with OTA led to microvilli disruption, tight junction protein (ZO-1 and claudin-1) damage, and inhibition of cell proliferation by arresting the cell cycle in the G2/M phase that promoted apoptosis. The treatment of B. subtilis CW14 mitigated the tight junction injury by improving ZO-1 protein expression, and it reduced apoptosis that was induced by OTA. Furthermore, transcriptome analysis indicated that OTA down-regulated genes that involved in the tight junction, cell cycle, and apoptosis-related signaling pathways. B. subtilis CW14 may have protected the ZO-1 protein by activating the toll-like receptor signaling pathway, and it reduced OTA damage by down-regulating the death receptor genes and up-regulating the DNA repair genes. These findings demonstrated the importance of B. subtilis CW14 in the regulation of tight junction proteins and in reducing death of intestinal epithelial cells. Thus, B. subtilis CW14 is a potential candidate as a food additive to protect against intestinal damage.

Keywords: Apoptosis; Bacillus subtilis; Cell cycle; Ochratoxin A; Tight junction; Toxicity.